BackgroundAdherence to nutritional guidelines for chronic disease prevention and management remains a challenge in clinical practice. Innovative strategies are needed to help optimise dietary behaviour change.ObjectiveThe objective of this study was to determine if a nutrigenomics-guided lifestyle intervention programme could be used to motivate greater dietary adherence and change in dietary intake short-term, moderate-term and long-term compared to the gold-standard population-based weight management intervention (Group Lifestyle Balance (GLB)/Diabetes Prevention Programme (DPP)).DesignThe Nutrigenomics, Overweight/Obesity, and Weight Management (NOW) randomised controlled trial is a pragmatic, parallel-group, superiority clinical trial (n=140), which was conducted at the East Elgin Family Health Team (EEFHT). GLB weight management groups were prerandomised 1:1 to receive either the standard GLB programme or a modified GLB+nutrigenomics (GLB+NGx) programme. Three 24-hour recalls were collected at baseline, 3, 6 and 12 months using the validated multiple pass method. Research assistants collecting the three 24-hour recalls were blinded to the participants’ group assignments. Statistical analyses included split plot analyses of variance (ANOVAs), two-way ANOVAs, binary logistic regression, χ2 and Fisher’s exact tests. Using the Theory of Planned Behaviour as guidance, key confounding factors of behaviour change were considered in the analyses. This study was registered with clinicaltrials.gov (NCT03015012).ResultsOnly the GLB+NGx group significantly reduced their total fat intake from baseline to 12-month follow-up (from 36.0%±4.8% kcal to 30.2%±8.7% kcal, p=0.02). Long-term dietary adherence to total fat and saturated fat guidelines was also significantly (p<0.05) greater in the GLB+NGx group compared to the standard GLB group.ConclusionsWeight management interventions guided by nutrigenomics can motivate long-term improvements in dietary fat intake above and beyond gold-standard population-based interventions.